March 9, 2005
By Ashley
Starkweather, B.S. and Asher Kimchi M.D.
Brooklyn, NY -
Intensive statin therapy was proven to reduce the risk of
cardiovascular events in patients with established coronary
artery disease and a current LDL level of less than
130mg/dl. The results of the double-blind, randomized trial
were published by John C. LaRosa, M.D., et. al, from the
State University of New York Health Science Center as an
early release on March 8, 2005 in the New England Journal of
Medicine. The findings were presented at this year’s
American College of Cardiology meeting in Orlando, Florida.
While the value of
reducing LDL cholesterol levels in preventing major
cardiovascular events has been well documented, the issue
has been raised as to what optimal treatment targets should
be. Prior to this study, the value in reducing LDL levels
below 100mg/dl in patients with coronary artery disease has
not been clearly proven.
Between July
1998 and December 1999 a total of 10,001 patients with
clinically evident coronary artery disease and LDL
cholesterol levels of less than 130mg/dl were randomly
assigned to double-blind therapy with either 10mg or 80mg
atorvastatin per day. Eligible patients were men and women
ages 35 to 75 years old who had clinically evident coronary
artery disease (CAD), defined by one or more of the
following: previous myocardial infarction, previous or
current angina with evidence of atherosclerotic CAD, and
history of revascularization.
Mean LDL
levels during the study were 77mg/dl in the 80mg
atorvastatin treatment group, and 101mg/dl in the 10mg
atorvastatin group.
The primary
efficacy endpoint was the occurrence of a major
cardiovascular event, defined as death from CAD, nonfatal
myocardial infarction, resuscitation after cardiac arrest,
or fatal or nonfatal stroke. A total of 434 patients in the
group given 80mg of atorvastatin and 548 patients in the
10mg group. This represented a 2.2 percent absolute
reduction in the 80mg group, with a 22 percent relative
reduction in the primary outcome (hazard ratio 0.78, 95
percent confidence interval 0.69 to 0.89, P<0.001). As
compared with patients given 10mg of atorvastatin, patients
in the 80mg group had significant reductions in the risk of
a major coronary event, any coronary event, cerebrovascular
events, hospitalization with a primary diagnosis of
congestive heart failure, and any cardiovascular event.
Furthermore,
the risk of death from any cause did not differ
significantly between the two drug regimens (hazard ratio
1.01, 95 percent confidence interval 0.85 to 1.19, P=0.92).
Adverse events related to treatment occurred in 8.1 percent
of patients on 80mg of atorvastatin, and in 5.8 percent of
patients on 10mg (P<0.001). These events included persistent
elevation in alanine aminotransferase, aspartate
aminotransferase, or both, and a few rare cases of
rhabdomyolysis. There were no persistent elevations in
creatine kinase.
The results
of this trial indicate that intensive therapy with 80mg of
atorvastatin to reduce LDL levels below 100mg/dl provides
significant clinical benefits in patients with established
coronary artery disease when compared to therapy at the 10mg
dose, with the only significant side effect being an
elevation in aminotransferase levels and occasional cases of
rhabdomyolysis.
Co-authors:
Scott M. Grundy, M.D., Ph.D., David D. Waters, M.D., Charles
Shear, Ph.D., Philip Barter, M.D., Ph.D., Jean-Charles
Fruchart, Pharm.D., Ph.D., Antonio M. Gotto, M.D., D.Phil.,
Heiner Greten, M.D., John J.P. Kastelein, M.D., James
Shepherd, M.D., Nanette K. Wenger, M.D.
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